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1. 发明申请

WO2009094485A1 METHODS AND ORGANISMS FOR UTILIZING SYNTHESIS GAS OR OTHER GASEOUS CARBON SOURCES AND METHANOL 审中-公开
标题翻译：使用合成气或其他气体碳源和甲醇的方法和有机体
公开(公告)号：WO2009094485A1
公开(公告)日：2009-07-30
申请号：PCT/US2009/031737
申请日：2009-01-22
申请人： GENOMATICA, INC. , BURK, Mark , SCHILLING, Christophe, H. , BURGARD, Anthony , TRAWICK, John, D.
发明人： BURK, Mark , SCHILLING, Christophe, H. , BURGARD, Anthony , TRAWICK, John, D.
IPC分类号： C12N1/20 , C12P21/06 , C12P11/00
CPC分类号： C12P7/18 , C12N9/0008 , C12N9/0036 , C12N9/1007 , C12N9/93 , C12N15/70 , C12P19/32 , Y02E50/343
摘要： The invention provides a non-naturally occurring microbial organism having an acetyl- CoA pathway and the capability of utilizing syngas or syngas and methanol. In one embodiment, the invention provides a non-naturally occurring microorganism, comprising one or more exogenous proteins conferring to the microorganism a pathway to convert CO, CO 2 and/or H 2 to acetyl-coenzyme A (acetyl-CoA), methyl tetrahydro folate (methyl-THF) or other desired products, wherein the microorganism lacks the ability to convert CO or CO 2 and H 2 to acetyl- CoA or methyl-THF in the absence of the one or more exogenous proteins. For example, the microbial organism can contain at least one exogenous nucleic acid encoding an enzyme or protein in an acetyl-CoA pathway. The microbial organism is capable of utilizing synthesis gases comprising CO, CO 2 and/or H 2 , alone or in combination with methanol, to produce acetyl- CoA. The invention additionally provides a method for producing acetyl-CoA, for example, by culturing an acetyl-CoA producing microbial organism, where the microbial organism expresses at least one exogenous nucleic acid encoding an acetyl-CoA pathway enzyme or protein in a sufficient amount to produce acetyl-CoA, under conditions and for a sufficient period of time to produce acetyl-CoA.
摘要翻译：本发明提供了具有乙酰辅酶A途径和利用合成气或合成气和甲醇的能力的非天然存在的微生物。在一个实施方案中，本发明提供非天然存在的微生物，其包含一种或多种外源蛋白质，赋予微生物将CO，CO 2和/或H 2转化为乙酰辅酶A（乙酰辅酶A），甲基四氢叶酸（甲基-THF）或其它所需产物，其中微生物缺乏在不存在一种或多种外源蛋白的情况下将CO或CO 2和H 2转化为乙酰辅酶A或甲基-THF的能力。例如，微生物生物体可以含有至少一种编码乙酰辅酶A途径中的酶或蛋白质的外源核酸。微生物生物能够单独或与甲醇组合使用包含CO，CO 2和/或H 2的合成气体，以产生乙酰辅酶A。本发明另外提供了生产乙酰辅酶A的方法，例如通过培养产生乙酰辅酶A的微生物，其中微生物生物体表达至少一种编码乙酰辅酶A途径酶或蛋白质的外源核酸，其量足够在条件和足够的时间内产生乙酰辅酶A产生乙酰辅酶A。

2. 发明申请

WO2008115840A2 COMPOSITIONS AND METHODS FOR THE BIOSYNTHESIS OF 1,4-BUTANEDIOL AND ITS PRECURSORS 审中-公开
标题翻译： 1,4-丁二醇及其前体的生物合成的组合物和方法
公开(公告)号：WO2008115840A2
公开(公告)日：2008-09-25
申请号：PCT/US2008/057168
申请日：2008-03-14
申请人： GENOMATICA, INC. , BURK, Mark, J. , VAN DIEN, Stephen, J. , BURGARD, Anthony , NIU, Wei
发明人： BURK, Mark, J. , VAN DIEN, Stephen, J. , BURGARD, Anthony , NIU, Wei
IPC分类号： C12N1/21
CPC分类号： C12N15/52 , B01D3/002 , C12N9/0006 , C12N9/0008 , C12N9/88 , C12N9/93 , C12N15/70 , C12N15/81 , C12P7/18 , C12P7/42 , C12P7/52 , C12P17/04 , C12Y101/01061 , C12Y102/01076 , C12Y401/01071 , C12Y602/01004 , Y02P20/52
摘要： The invention provides a non-naturally occurring microbial biocatalyst including a microbial organism having a 4-hydroxybutanoic acid (4-HB) biosynthetic pathway having at least one exogenous nucleic acid encoding 4-hydroxybutanoate dehydrogenase, succinyl-CoA synthetase, CoA-dependent succinic semialdehyde dehydrogenase, or α-ketoglutarate decarboxylase, wherein the exogenous nucleic acid is expressed in sufficient amounts to produce monomeric 4-hydroxybutanoic acid (4-HB). Also provided is a non-naturally occurring microbial biocatalyst including a microbial organism having 4-hydroxybutanoic acid (4-HB) and 1,4-butanediol (BDO) biosynthetic pathways, the pathways include at least one exogenous nucleic acid encoding 4-hydroxybutanoate dehydrogenase, succinyl-CoA synthetase, CoA-dependent succinic semialdehyde dehydrogenase, 4-hydroxybutyrate:CoA transferase, 4-butyrate kinase, phosphotransbutyrylase, α-ketoglutarate decarboxylase, aldehyde dehydrogenase, alcohol dehydrogenase or an aldehyde/alcohol dehydrogenase, wherein the exogenous nucleic acid is expressed in sufficient amounts to produce 1,4- butanediol (BDO). Additionally provided is a method for the production of 4-HB. The method includes culturing a non-naturally occurring microbial organism having a A- hydroxybutanoic acid (4-HB) biosynthetic pathway including at least one exogenous nucleic acid encoding 4-hydroxybutanoate dehydrogenase, succinyl-CoA synthetase, CoA-dependent succinic semialdehyde dehydrogenase or α-ketoglutarate decarboxylase under substantially anaerobic conditions for a sufficient period of time to produce monomeric A- hydroxybutanoic acid (4-HB). Further provided is a method for the production of BDO. The method includes culturing a non-naturally occurring microbial biocatalyst, comprising a microbial organism having 4-hydroxybutanoic acid (4-HB) and 1,4-butanediol (BDO) biosynthetic pathways, the pathways including at least one exogenous nucleic acid encoding 4-hydroxybutanoate dehydrogenase, succinyl-CoA synthetase, CoA-dependent succinic semialdehyde dehydrogenase, 4-hydroxybutyrate:CoA transferase, 4-hydroxybutyrate kinase, phosphotranshydroxybutyrylase, α-ketoglutarate decarboxylase, aldehyde dehydrogenase, alcohol dehydrogenase or an aldehyde/alcohol dehydrogenase for a sufficient period of time to produce 1,4-butanediol (BDO). The 4-HB and/or BDO products can be secreted into the culture medium.
摘要翻译：本发明提供一种非天然存在的微生物生物催化剂，其包括具有4-羟基丁酸（4-HB）生物合成途径的微生物生物，其具有至少一种编码4-羟基丁酸脱氢酶的外源核酸，琥珀酰辅酶A合成酶，CoA依赖性琥珀酸半醛脱氢酶或α-酮戊二酸脱羧酶，其中外源核酸以足够的量表达以产生单体4-羟基丁酸（4-HB）。还提供了非天然存在的微生物生物催化剂，其包括具有4-羟基丁酸（4-HB）和1,4-丁二醇（BDO）生物合成途径的微生物生物，该途径包括至少一种编码4-羟基丁酸脱氢酶的外源核酸，琥珀酰辅酶A合成酶，CoA依赖性琥珀酸半醛脱氢酶，4-羟基丁酸酯：CoA转移酶，4-丁酸激酶，磷酸转移酶，α-酮戊二酸脱羧酶，醛脱氢酶，醇脱氢酶或醛/醇脱氢酶，其中外源核酸为表达量足以生产1,4-丁二醇（BDO）。另外提供了用于生产4-HB的方法。所述方法包括培养具有4-羟基丁酸（4-HB）生物合成途径的非天然存在的微生物生物，其包含至少一种编码4-羟基丁酸脱氢酶的外源核酸，琥珀酰辅酶A合成酶，辅酶A依赖性琥珀酸半醛脱氢酶或 - 酮戊二酸脱羧酶在充分的厌氧条件下持续足够的时间以产生单体的4-羟基丁酸（4-HB）。进一步提供一种生产BDO的方法。该方法包括培养非天然存在的微生物生物催化剂，其包含具有4-羟基丁酸（4-HB）和1,4-丁二醇（BDO）生物合成途径的微生物生物，所述途径包括至少一种编码4- 羟基丁酸脱氢酶，琥珀酰辅酶A合成酶，CoA依赖性琥珀酸脱氢酶，4-羟基丁酸酯：CoA转移酶，4-羟基丁酸酯激酶，磷酸转移羟基丁酸酶，α-酮戊二酸脱羧酶，醛脱氢酶，醇脱氢酶或醛/醇脱氢酶，时间来生产1,4-丁二醇（BDO）。 4-HB和/或BDO产物可以分泌到培养基中。

3. 发明公开

EP2245137A1 METHODS AND ORGANISMS FOR UTILIZING SYNTHESIS GAS OR OTHER GASEOUS CARBON SOURCES AND METHANOL 有权转让
标题翻译：方法和机构使用合成气或其它气态碳源甲醇
公开(公告)号：EP2245137A1
公开(公告)日：2010-11-03
申请号：EP09704131.3
申请日：2009-01-22
申请人： Genomatica, Inc.
发明人： BURK, Mark , SCHILLING, Christophe, H. , BURGARD, Anthony , TRAWICK, John, D.
IPC分类号： C12N1/20 , C12P21/06 , C12P11/00
CPC分类号： C12P7/18 , C12N9/0008 , C12N9/0036 , C12N9/1007 , C12N9/93 , C12N15/70 , C12P19/32 , Y02E50/343
摘要： The invention provides a non-naturally occurring microbial organism having an acetyl-CoA pathway and the capability of utilizing syngas or syngas and methanol. In one embodiment, the invention provides a non-naturally occurring microorganism, comprising one or more exogenous proteins conferring to the microorganism a pathway to convert CO, CO2 and/or H2 to acetyl-coenzyme A (acetyl-CoA), methyl tetrahydrofolate (methyl-THF) or other desired products, wherein the microorganism lacks the ability to convert CO or CO2 and H2 to acetyl-CoA or methyl-THF in the absence of the one or more exogenous proteins. For example, the microbial organism can contain at least one exogenous nucleic acid encoding an enzyme or protein in an acetyl-CoA pathway. The microbial organism is capable of utilizing synthesis gases comprising CO, CO2 and/or H2, alone or in combination with methanol, to produce acetyl-CoA. The invention additionally provides a method for producing acetyl-CoA, for example, by culturing an acetyl-CoA producing microbial organism, where the microbial organism expresses at least one exogenous nucleic acid encoding an acetyl-CoA pathway enzyme or protein in a sufficient amount to produce acetyl-CoA, under conditions and for a sufficient period of time to produce acetyl-CoA.

4. 发明授权

EP2137315B1 COMPOSITIONS AND METHODS FOR THE BIOSYNTHESIS OF 1,4-BUTANEDIOL AND ITS PRECURSORS 有权转让
标题翻译：组合物和生物合成1,4-丁二醇及其前体的方法
公开(公告)号：EP2137315B1
公开(公告)日：2014-09-03
申请号：EP08732315.0
申请日：2008-03-14
申请人： Genomatica, Inc.
发明人： BURK, Mark, J. , VAN DIEN, Stephen, J. , BURGARD, Anthony , NIU, Wei
IPC分类号： C12P7/18
CPC分类号： C12N15/52 , B01D3/002 , C12N9/0006 , C12N9/0008 , C12N9/88 , C12N9/93 , C12N15/70 , C12N15/81 , C12P7/18 , C12P7/42 , C12P7/52 , C12P17/04 , C12Y101/01061 , C12Y102/01076 , C12Y401/01071 , C12Y602/01004 , Y02P20/52
摘要： The invention provides a non-naturally occurring microbial biocatalyst including a microbial organism having a 4-hydroxybutanoic acid (4-HB) biosynthetic pathway having at least one exogenous nucleic acid encoding 4-hydroxybutanoate dehydrogenase, succinyl-CoA synthetase, CoA-dependent succinic semialdehyde dehydrogenase, or ±-ketoglutarate decarboxylase, wherein the exogenous nucleic acid is expressed in sufficient amounts to produce monomeric 4-hydroxybutanoic acid (4-HB). Also provided is a non-naturally occurring microbial biocatalyst including a microbial organism having 4-hydroxybutanoic acid (4-HB) and 1,4-butanediol (BDO) biosynthetic pathways, the pathways include at least one exogenous nucleic acid encoding 4-hydroxybutanoate dehydrogenase, succinyl-CoA synthetase, CoA-dependent succinic semialdehyde dehydrogenase, 4-hydroxybutyrate:CoA transferase, 4-butyrate kinase, phosphotransbutyrylase, ±-ketoglutarate decarboxylase, aldehyde dehydrogenase, alcohol dehydrogenase or an aldehyde/alcohol dehydrogenase, wherein the exogenous nucleic acid is expressed in sufficient amounts to produce 1,4-butanediol (BDO). Additionally provided is a method for the production of 4-HB. The method includes culturing a non-naturally occurring microbial organism having a 4-hydroxybutanoic acid (4-HB) biosynthetic pathway including at least one exogenous nucleic acid encoding 4-hydroxybutanoate dehydrogenase, succinyl-CoA synthetase, CoA-dependent succinic semialdehyde dehydrogenase or ±-ketoglutarate decarboxylase under substantially anaerobic conditions for a sufficient period of time to produce monomeric 4-hydroxybutanoic acid (4-HB). Further provided is a method for the production of BDO. The method includes culturing a non-naturally occurring microbial biocatalyst, comprising a microbial organism having 4-hydroxybutanoic acid (4-HB) and 1,4-butanediol (BDO) biosynthetic pathways, the pathways including at least one exogenous nucleic acid encoding 4-hydroxybutanoate dehydrogenase, succinyl-CoA synthetase, CoA-dependent succinic semialdehyde dehydrogenase, 4-hydroxybutyrate:CoA transferase, 4-hydroxybutyrate kinase, phosphotranshydroxybutyrylase, ±-ketoglutarate decarboxylase, aldehyde dehydrogenase, alcohol dehydrogenase or an aldehyde/alcohol dehydrogenase for a sufficient period of time to produce 1,4-butanediol (BDO). The 4-HB and/or BDO products can be secreted into the culture medium.

5. 发明授权

EP2245137B1 METHODS AND ORGANISMS FOR UTILIZING SYNTHESIS GAS OR OTHER GASEOUS CARBON SOURCES AND METHANOL 有权转让
标题翻译：使用合成气体或其他气态碳源和甲醇的方法和生物
公开(公告)号：EP2245137B1
公开(公告)日：2017-08-16
申请号：EP09704131.3
申请日：2009-01-22
申请人： Genomatica, Inc.
发明人： BURK, Mark , SCHILLING, Christophe, H. , BURGARD, Anthony , TRAWICK, John, D.
IPC分类号： C12N1/20 , C12P21/06 , C12P11/00
CPC分类号： C12P7/18 , C12N9/0008 , C12N9/0036 , C12N9/1007 , C12N9/93 , C12N15/70 , C12P19/32 , Y02E50/343
摘要： The invention provides a non-naturally occurring microbial organism having an acetyl-CoA pathway and the capability of utilizing syngas or syngas and methanol. In one embodiment, the invention provides a non-naturally occurring microorganism, comprising one or more exogenous proteins conferring to the microorganism a pathway to convert CO, CO2 and/or H2 to acetyl-coenzyme A (acetyl-CoA), methyl tetrahydrofolate (methyl-THF) or other desired products, wherein the microorganism lacks the ability to convert CO or CO2 and H2 to acetyl-CoA or methyl-THF in the absence of the one or more exogenous proteins. For example, the microbial organism can contain at least one exogenous nucleic acid encoding an enzyme or protein in an acetyl-CoA pathway. The microbial organism is capable of utilizing synthesis gases comprising CO, CO2 and/or H2, alone or in combination with methanol, to produce acetyl-CoA. The invention additionally provides a method for producing acetyl-CoA, for example, by culturing an acetyl-CoA producing microbial organism, where the microbial organism expresses at least one exogenous nucleic acid encoding an acetyl-CoA pathway enzyme or protein in a sufficient amount to produce acetyl-CoA, under conditions and for a sufficient period of time to produce acetyl-CoA.
摘要翻译：本发明提供具有乙酰-CoA途径和利用合成气或合成气和甲醇的能力的非天然存在的微生物。在一个实施方案中，本发明提供了非天然存在的微生物，其包含一种或多种赋予微生物CO，CO 2和/或H 2转化为乙酰辅酶A（乙酰-CoA），甲基四氢叶酸（甲基 -THF）或其他所需产物，其中所述微生物缺乏在不存在所述一种或多种外源蛋白质的情况下将CO或CO 2和H 2转化成乙酰-CoA或甲基-THF的能力。例如，微生物生物体可以含有编码乙酰-CoA途径中的酶或蛋白质的至少一种外源核酸。微生物生物体能够单独或与甲醇组合使用包含CO，CO 2和/或H 2的合成气体来产生乙酰-CoA。本发明另外提供了例如通过培养产生乙酰-CoA的微生物有机体来生产乙酰-CoA的方法，其中所述微生物有机体表达编码乙酰-CoA途径酶或蛋白质的至少一种外源性核酸，其量足以在一定条件下和产生乙酰-CoA的条件下产生乙酰-CoA。

6. 发明公开

EP2137315A2 COMPOSITIONS AND METHODS FOR THE BIOSYNTHESIS OF 1,4-BUTANEDIOL AND ITS PRECURSORS 有权转让
标题翻译：组合物和生物合成1,4-丁二醇及其前体的方法
公开(公告)号：EP2137315A2
公开(公告)日：2009-12-30
申请号：EP08732315.0
申请日：2008-03-14
申请人： Genomatica, Inc.
发明人： BURK, Mark, J. , VAN DIEN, Stephen, J. , BURGARD, Anthony , NIU, Wei
IPC分类号： C12P1/00
CPC分类号： C12N15/52 , B01D3/002 , C12N9/0006 , C12N9/0008 , C12N9/88 , C12N9/93 , C12N15/70 , C12N15/81 , C12P7/18 , C12P7/42 , C12P7/52 , C12P17/04 , C12Y101/01061 , C12Y102/01076 , C12Y401/01071 , C12Y602/01004 , Y02P20/52
摘要： The invention provides a non-naturally occurring microbial biocatalyst including a microbial organism having a 4-hydroxybutanoic acid (4-HB) biosynthetic pathway having at least one exogenous nucleic acid encoding 4-hydroxybutanoate dehydrogenase, succinyl-CoA synthetase, CoA-dependent succinic semialdehyde dehydrogenase, or ±-ketoglutarate decarboxylase, wherein the exogenous nucleic acid is expressed in sufficient amounts to produce monomeric 4-hydroxybutanoic acid (4-HB). Also provided is a non-naturally occurring microbial biocatalyst including a microbial organism having 4-hydroxybutanoic acid (4-HB) and 1,4-butanediol (BDO) biosynthetic pathways, the pathways include at least one exogenous nucleic acid encoding 4-hydroxybutanoate dehydrogenase, succinyl-CoA synthetase, CoA-dependent succinic semialdehyde dehydrogenase, 4-hydroxybutyrate:CoA transferase, 4-butyrate kinase, phosphotransbutyrylase, ±-ketoglutarate decarboxylase, aldehyde dehydrogenase, alcohol dehydrogenase or an aldehyde/alcohol dehydrogenase, wherein the exogenous nucleic acid is expressed in sufficient amounts to produce 1,4-butanediol (BDO). Additionally provided is a method for the production of 4-HB. The method includes culturing a non-naturally occurring microbial organism having a 4-hydroxybutanoic acid (4-HB) biosynthetic pathway including at least one exogenous nucleic acid encoding 4-hydroxybutanoate dehydrogenase, succinyl-CoA synthetase, CoA-dependent succinic semialdehyde dehydrogenase or ±-ketoglutarate decarboxylase under substantially anaerobic conditions for a sufficient period of time to produce monomeric 4-hydroxybutanoic acid (4-HB). Further provided is a method for the production of BDO. The method includes culturing a non-naturally occurring microbial biocatalyst, comprising a microbial organism having 4-hydroxybutanoic acid (4-HB) and 1,4-butanediol (BDO) biosynthetic pathways, the pathways including at least one exogenous nucleic acid encoding 4-hydroxybutanoate dehydrogenase, succinyl-CoA synthetase, CoA-dependent succinic semialdehyde dehydrogenase, 4-hydroxybutyrate:CoA transferase, 4-hydroxybutyrate kinase, phosphotranshydroxybutyrylase, ±-ketoglutarate decarboxylase, aldehyde dehydrogenase, alcohol dehydrogenase or an aldehyde/alcohol dehydrogenase for a sufficient period of time to produce 1,4-butanediol (BDO). The 4-HB and/or BDO products can be secreted into the culture medium.

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